Fibrosis involves the abnormal accumulation of extracellular matrix proteins and disrupted tissue repair, resulting in permanent scar tissue due to injury. Exosomes, tiny vesicles containing signaling molecules like mRNAs and proteins, are secreted by epithelial cells at injury sites. These molecules activate fibroblasts, enhancing their migration, proliferation, and contraction, leading to tissue repair. However, in the case of repetitive injury, these properties are abnormally activated and lead to fibrosis. Consequently, fibrotic diseases can lead to organ failure and eventually death, making early diagnosis crucial. Despite understanding fibrosis pathology and mechanisms, translating anti-fibrosis targets into effective therapies remains challenging.
Wang et al. have highlighted the critical role of epithelial-derived exosomes in the fibrotic process and the potential diagnostic and therapeutic value of the bioactive molecules they carry. The miR-451a (microRNA molecules) found in epithelial-derived exosomes can mitigate pulmonary fibrosis, suggesting that harnessing exosomes to deliver miRNAs is a viable strategy for treating this condition. Conversely, miR-210 exacerbates fibrosis formation. Scientists have discovered that AGT7, a gene associated with autophagy, is directly regulated by miR-210. By targeting AGT7, miR-210 modulates autophagy and accelerates myofibroblast differentiation. Thus, exosomal miR-210 can regulate myofibroblast differentiation and serve as a marker for COPD.
Similarly, in skin, renal, or cardiac fibrosis, regulating miRNAs in exosomes and leveraging their effects can yield significant antifibrotic outcomes. Researchers have also demonstrated that exosomes, due to their lipid bilayer membranes, can serve as efficient drug delivery vehicles. Their bioactive protein molecules remain stable in body fluids, and they can easily penetrate tissues, exhibiting low immunogenicity and toxicity.
Therefore, identifying appropriate exosomal proteins could provide valuable biomarkers for diagnosing and treating fibrosis in translational medicine. For example, in acute liver injury, stem cell-derived exosomes can reduce hepatocyte apoptosis, alleviate oxidative stress, and decrease tissue inflammation infiltration, thereby mitigating renal failure. Additionally, neuronal exosomes can serve as valuable biomarkers for Alzheimer’s disease by tracking cognitive performance changes and hold promise in tumor immunogenicity applications.
In summary, epithelial-derived exosomes emerge as pivotal regulators in fibrotic processes, influencing effector cell activation, signaling molecule expression, and associated pathways crucial for fibrosis development. Their unique characteristics offer promising avenues for diagnosing and treating fibrotic diseases, with ongoing modifications expected to enhance clinical treatments. However, challenges persist in translating exosome efficacy into clinical practice, including the need for elucidating precise molecular loading and mechanisms, standardizing extraction and characterization processes, and addressing heterogeneity in dosage and administration methods across trials. Overcoming these obstacles through further research is imperative to realize the full potential of exosomes as a therapeutic strategy for fibrotic disorders, paving the way for improved diagnostic and therapeutic approaches in the future.
Author: Ebrar Yolcu
Editor: Elif Duymaz
Reference: Wang, R., Shi, Y., Lv, Y., Xie, C., & Hu, Y. (2024, May 1). The novel insights of epithelial-derived exosomes in various fibrotic diseases. Biomedicine & Pharmacotherapy. https://doi.org/10.1016/j.biopha.2024.116591
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